Traumatic events in childhood and stress or emotional instability at any period in life may be associated with the development of chronic fatigue syndrome (CFS), according to two articles in the November issue of Archives of General Psychiatry, one of the JAMA/Archives journals. The findings suggest that CFS and similar illnesses may result from the brain's inability to cope with challenging experiences.

CFS affects between 400,000 and 900,000 U.S. adults, according to background information in the article. The condition is defined as unexplained fatigue that lasts for at least six months, does not get better with rest and interferes with daily activities. For a formal diagnosis of CFS, fatigue must be accompanied by at least four of eight additional symptoms, including extreme fatigue after exertion, difficulties with memory and concentration, unrefreshing sleep, headaches, muscle pain, joint pain, sore throat and tender lymph nodes. "Despite the substantial public burden of CFS, the causes and pathophysiology [underlying changes] of CFS remain unknown, and effective prevention is elusive," the authors of the first article write.

Christine Heim, Ph.D., Centers for Disease Control and Prevention and Emory University, Atlanta, and colleagues compared 43 individuals with CFS to 60 controls without CFS who were all part of a large study of Wichita, Kansas, residents. All participants (average age 50.5) underwent a medical examination and provided their medical history, and were interviewed to detect psychiatric disorders. They then responded to a questionnaire that assessed for five types of childhood trauma: emotional, physical and sexual abuse and emotional and physical neglect. Responses to each item were numbered and added to produce a score for each type of trauma and one overall trauma score.

Individuals with CFS had higher overall trauma scores than those without CFS. Exposure to trauma increased the risk of CFS between three and eight times, depending on the type; emotional neglect and sexual abuse during childhood were most strongly associated with CFS. For each additional type of childhood trauma experienced, the risk of having CRS increased by 77 percent; the risk increased by 6 percent for each additional point increase in total trauma score. Not all patients with CFS had experienced childhood trauma, but those who had tended to have worse symptoms than those who had not.

CFS patients were also more likely than controls to have psychiatric disorders, including depression, anxiety and post-traumatic stress disorder. These conditions appeared to be associated with childhood trauma. "In sum, it appears that CFS is part of a spectrum of disorders that are associated with childhood adversity," the authors write. "In adulthood, these disorders frequently manifest or worsen in relation to an acute stress or challenge. High emotional reactivity is a risk factor for all of these disorders. Thus, enhanced stress and mood reactivity can be assumed to be a central feature common to this spectrum of disorders.

"In fact, these disorders might reflect the brain's inability to adapt or compensate in response to challenge, leading toward maladaptive responses and ultimately disease," they conclude.

In the second study, Kenji Kato, Ph.D., Karolinska Institutet, Stockholm, Sweden, and colleagues assessed 19,192 Swedish twins born between 1935 and 1958, 1,570 of whom had chronic fatigue. Of those, 1,120 were impaired by their fatigue and 447 had the necessary four additional symptoms of CFS; these two groups were categorized as having CFS for the purposes of the study. Between 1972 and 1973, all participants answered questions about their personalities--which researchers assessed in terms of emotional stability and extraversion--and one question about stress: "Do you experience your daily existence as being very 'stress filled'?" Three analyses were performed: One that matched each of the 1,567 individuals with CFS to individuals of the same age and sex without CFS; one that compared those with CFS to their twins without CFS, regardless of whether twins were identical or fraternal; and one that compared only identical twins with CFS to their co-twins without CFS.

In the first two analyses, emotional instability--defined as "an individual's tendency to experience psychological distress that can be reliably measured by self-report and is relatively stable in an individual over time"--and stress were associated with CFS, while extraversion was not. In the age- and sex-matched comparison, individuals who reported that their life was stressful were 64 to 65 percent more likely to develop CFS; in the analysis comparing twins, the risk increased to 500 percent. "This suggests that some genes may serve as a buffering effect whereas other sensitive individuals are more susceptible to the impact of stress," the authors write.

When only identical twins were assessed, emotional instability was not linked to risk for CFS, indicating that similar genetic factors underlie both conditions. "In contrast to stress, the association between emotional instability and fatigue is more likely to be endogenous," or without an external cause, the authors continue. "Because we found considerable influences attributable to genetic and early environmental factors, our results suggest biological mechanisms that mediate the relationship between emotional instability and chronic fatigue. Likely candidates are those genes related to neurotransmission that have been implicated in depression and emotional instability."

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